A study of the molecular structure of proteins binding cadmium in rat lungs and kidneys following toxic inhalation exposures will be undertaken. Special emphasis will be placed on characterizing the molecular structure surrounding the metal. The relationship between cadmium and the interacting macromolecules will be investigated in order to understand the mechanism of toxicity (mechanism of action) of the metal. Pulse and Fourier Transform nuclear magnetic resonance (NMR), and other spectroscopic techniques will be used to probe the immediate environment around cadmium, as well as the structure of the small molecules. The subcellular distribution pattern of cadmium in normal lungs and those subjected to chronic inhalation exposures of cadmium oxide has been established in these laboratories. The cumulative data demonstrates a shift of cadmium, normally associated with the connective tissue and cell membranes of the lung, into the cell cytoplasm where is is associated primarily with a low molecular weight, metallothionein- like protein in the lung. In the kidney the distribution ratio lies between a protein resembling metallothionein and a lower molecular weight polypeptide. Further effort will be expended to separate and structurally elucidate the molecular components to which cadmium is bound. Established purification procedures such as gel filtration chromatography and isoelectric focusing will be employed to obtain electrophoretically and ultracentrifugally homogenous components, primarily low molecular weight molecules. Standard biochemical tests such as sulfhydryl and protein determinations, as well as amino acid analyses and ultraviolet absorption monitoring of the metal-sulfur charge transfer band will be performed.